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Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.

Cao Y, Gao Y, Xu S, Bao J, Lin Y, Luo X, Wang Y, Luo Q, Jiang J, Neale JH, Zhong C - BMC Neurosci (2016)

Bottom Line: Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury.Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde.These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

ABSTRACT

Background: Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system.

Results: Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice.

Conclusions: These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

No MeSH data available.


Related in: MedlinePlus

GCP II KO inhibited TBI-induced apoptosis. a Representative TUNEL-staining (green) and DAPI-stained (blue) brain sections of the penumbra area at 1.4 mm from the bregma (magnification ×200). The scale bar is 100 μm. b Quantification showed that GCP II KO markedly decreased the apoptotic index after TBI compared to the WT TBI mice. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured wild-type mice
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Fig2: GCP II KO inhibited TBI-induced apoptosis. a Representative TUNEL-staining (green) and DAPI-stained (blue) brain sections of the penumbra area at 1.4 mm from the bregma (magnification ×200). The scale bar is 100 μm. b Quantification showed that GCP II KO markedly decreased the apoptotic index after TBI compared to the WT TBI mice. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured wild-type mice

Mentions: TUNEL staining was performed to assess TBI-induced cell apoptosis. TUNEL-positive nuclei were not observed in both sham TBI groups (Fig. 2). The number of apoptotic cells in the contusion margin significantly increased in the TBI groups (both p < 0.05, n = 6). GCPII KO significantly diminished the number of TUNEL-positive nuclei in the cortex surrounding the injury core (p < 0.05, n = 6).Fig. 2


Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.

Cao Y, Gao Y, Xu S, Bao J, Lin Y, Luo X, Wang Y, Luo Q, Jiang J, Neale JH, Zhong C - BMC Neurosci (2016)

GCP II KO inhibited TBI-induced apoptosis. a Representative TUNEL-staining (green) and DAPI-stained (blue) brain sections of the penumbra area at 1.4 mm from the bregma (magnification ×200). The scale bar is 100 μm. b Quantification showed that GCP II KO markedly decreased the apoptotic index after TBI compared to the WT TBI mice. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured wild-type mice
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836105&req=5

Fig2: GCP II KO inhibited TBI-induced apoptosis. a Representative TUNEL-staining (green) and DAPI-stained (blue) brain sections of the penumbra area at 1.4 mm from the bregma (magnification ×200). The scale bar is 100 μm. b Quantification showed that GCP II KO markedly decreased the apoptotic index after TBI compared to the WT TBI mice. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured wild-type mice
Mentions: TUNEL staining was performed to assess TBI-induced cell apoptosis. TUNEL-positive nuclei were not observed in both sham TBI groups (Fig. 2). The number of apoptotic cells in the contusion margin significantly increased in the TBI groups (both p < 0.05, n = 6). GCPII KO significantly diminished the number of TUNEL-positive nuclei in the cortex surrounding the injury core (p < 0.05, n = 6).Fig. 2

Bottom Line: Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury.Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde.These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

ABSTRACT

Background: Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system.

Results: Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice.

Conclusions: These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

No MeSH data available.


Related in: MedlinePlus